Efficacy Analysis From Phase I Study of Lorvotuzumab Mertansine (IMGN901), Used as Monotherapy, In Patients with Heavily Pre-Treated CD56-Positive Multiple Myeloma - A Preliminary Efficacy Analysis
Notice bibliographique
Résumé
Abstract Abstract 1962 Background: Lorvotuzumab mertansine, also known as IMGN901 (huN901-DM1/BB-10901) is a novel anticancer agent consisting of a potent cytotoxic maytansinoid, DM1, attached to a CD56-binding monoclonal antibody, lorvotuzumab, using an engineered linker. Once bound to CD56 on a cancer cell and internalized, the DM1 is released to kill the cancer cell. Greater than 70% of multiple myeloma (MM) cases have surface expression of CD56. Safety information from the dose-escalation phase of this study was reported (ASH 114:2883, 2009) as the study was entering its expansion phase. Objectives: This study is designed to determine the MTD, pharmacokinetics (PK), and activity of IMGN901 used as monotherapy in patients with CD56+ MM, with additional information on its safety and efficacy to be obtained from its expansion phase. Methods: Patients with CD56+ relapsed or relapsed/refractory MM receive a single IV infusion of IMGN901 weekly for 2 consecutive weeks every 3 weeks. During the dose-escalation phase, patients were enrolled into each dose level in cohorts of 3, with dose-limiting toxicity (DLT) triggering cohort expansion. Once the MTD was determined, an expansion cohort was opened to further characterize the safety and efficacy of IMGN901 administered at its MTD. Results: Thirty-seven CD56+ MM patients have received IMGN901 at doses ranging from 40 to 140 mg/m2/week with 19 patients treated at the MTD of 112 mg/m2. Most of these 37 patients had been treated with 6 or more chemotherapy regimens prior to study entry. Among the 28 evaluable patients, 13 received IMGN901 treatment for more than three months, with 2 remaining on treatment for more than a year. Five of these patients achieved an objective response (OR) according to the European Bone Marrow Transplant Criteria – 2 partial responses and 3 minimal responses. The clinical benefit rate approximates 46%. Three patients have experienced four grade 3 drug-related toxicities that are considered at least possibly related to IMGN901: fatigue, renal failure, weakness, and absence of deep tendon reflexes. No grade 4 drug-related toxicities have been reported. No patients have demonstrated a humoral response against either the antibody or DM1 component of IMGN901. Conclusion: In this population of patients with heavily pretreated MM, IMGN901 demonstrates an ability to provide sustained clinical benefit and tolerability. This warrants its continued investigation as monotherapy and supports its investigation as part of a combination regimen. Disclosures: Jagannath: Millennium: Honoraria; Orthobiotec (Canada): Honoraria; Celgene: Honoraria; Merck: Honoraria; Onyx Pharma: Honoraria; Proteolix: Honoraria; Imedex: Membership on an entity's Board of Directors or advisory committees; Medicom World Wide: Membership on an entity's Board of Directors or advisory committees; Optum Health Education: Membership on an entity's Board of Directors or advisory committees; PER Group: Membership on an entity's Board of Directors or advisory committees. Zildjian:ImmunoGen, Inc.: Employment. O'Leary:ImmunoGen, Inc.: Employment.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».